Ashi, A., Awaji, A.A., Bond, J. orcid.org/0000-0001-5390-5688 et al. (3 more authors) (2025) Threonine and tyrosine kinase (TTK) mRNA and protein expression in breast cancer; prognostic significance in the neoadjuvant setting. Histopathology. ISSN 0309-0167
Abstract
Aims
Threonine and tyrosine kinase (TTK) is up-regulated in triple-negative breast cancer (TNBC), yet its expression in patients undergoing neoadjuvant chemotherapy (NACT) remains unexplored. This investigation aims to assess TTK protein expression in treatment-naïve pre-treatment cores and paired pre- and post-NACT breast cancer (BC) cohorts, as well as its correlation with microcephaly 1 (MCPH1) protein expression.
Methods and results
Transcriptomic data were sourced from the Gene Expression Omnibus microarray database for mRNA expression analysis. TTK protein expression was evaluated using immunohistochemistry staining, employing receiver operating characteristic curve analysis to determine an optimal TTK expression cut-off point. The association between TTK expression, clinicopathological parameters and survival outcomes was examined. Additionally, MCPH1 protein expression was assessed in a pilot study. Analysis revealed a significantly elevated TTK mRNA expression in BC tissue compared to normal breast tissue, with high TTK mRNA levels predicting reduced overall survival. Notably, TTK protein expression increased significantly post-NACT in a paired cohort. Conversely, decreased TTK protein expression pre-NACT was correlated with improved overall survival.
Conclusions
High TTK and low MCPH1 protein expression was significantly correlated, highlighting TTK's potential as a biomarker for BC and a therapeutic target for MCPH1-deficient cancer cells.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Author(s). Histopathology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | breast cancer, MCPH1, neoadjuvant chemotherapy (NACT), TNBC, TTK |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Medical Research (LIMR) > Division of Molecular Medicine |
Funding Information: | Funder Grant number Leeds Teaching Hospitals Special Trust 3u65/9240 |
Depositing User: | Symplectic Publications |
Date Deposited: | 14 Jan 2025 11:49 |
Last Modified: | 14 Jan 2025 11:49 |
Published Version: | https://onlinelibrary.wiley.com/doi/10.1111/his.15... |
Status: | Published online |
Publisher: | Wiley |
Identification Number: | 10.1111/his.15399 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:221761 |